The objectives of the Molecular Mechanisms of Toxicity Training Program are to provide trainees with an education in the cellular and molecular mechanisms by which environmental agents induce human disease. The training program is based on an understanding of biochemistry, molecular/cell biology, pharmacology, and toxicology, and is coupled with in-depth laboratory research training. The Training Program is based in the Graduate Center for Toxicology (GCT), a basic science department in the College of Medicine that grants the Ph.D. in Toxicology and provides an administrative and teaching nucleus of 11 Core Faculty. Joint faculty from Medicine, Pharmacy, Agriculture, and Arts &Sciences enrich the diversity of training opportunities;25 of these Core and Joint Faculty with strong research programs make up the Training Grant Faculty. This competitive renewal application requests support for 4 pre- and 2 postdoctoral trainees;it is focused on three disease areas with an environmental basis: Cancer, Cardiovascular Disease and Neurodegenerative Disease. Oxidative stress and DNA damage and repair are mechanistic themes that underlie many of the research programs, providing opportunities for collaborations and multidisciplinary approaches that enrich the research training. The pre-doctoral training program requires biomedical (25 credits) and toxicology bases (13 credits) and an elective (2-4 credits). Pre-doctoral trainees will be supported for a maximum of 3 years (e.g., years 2-4 of doctoral training;Postdoctoral trainees will be supported for a minimum of 2 years. Ph.D. fellows will be recruited within 3 years of their degree, while M.D. fellows will be recruited upon completion of their residency training;the investigators anticipate a ratio of 2 Ph.D.s to 1 M.D. Postdoctoral trainees are required to enroll and participate in 2 credits of Environmental Exposure and Human Disease in addition to a rigorous laboratory experience. Currently, 28 students are enrolled in the Toxicology Ph.D. program, including 6 minority students, most of whom were recruited from the University of Puerto Rico and supported by summer research/education grants. The University provides strong support for the GCT in the form of student fellowships, supplementation to this Training Grant, and faculty lines, space and equipment to enhance and sustain a strong toxicology program. Relevance: The Training Program in Molecular Mechanisms of Toxicity will provide pre- and postdoctoral fellows with a fundamental understanding of the molecular and cellular processes by which environmental agents impact human health and cause disease. The long-term goal is to prepare and inspire the next generation of scientists to address the ever-present environmental challenges to human health by the prevention of disease, either by nutritional intervention or by otherwise exploiting human defense systems.